The dioxygenase TET2 regulates pathological cardiac hypertrophy

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-08-13 DOI:10.1016/j.lfs.2025.123915

Wenxuan Hong , Yuwen Zhu , Mengwen Qi , Xiaoyan Wang , Mingming Fang

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引用次数: 0

Abstract

Aims

Heart failure (HF) is one of the most devastating consequences of cardiovascular diseases. Regardless of etiology, heart failure is often preceded by cardiac hypertrophy. In the present study we investigated the effect of cardiomyocyte-specific deletion of ten-and-eleven translocation 2 (TET2) on cardiac hypertrophy.

Methods and materials

Cardiac hypertrophy was induced in vitro by exposing cardiomyocytes to angiotensin II (Ang II), isoproterenol (ISO), or phenyleprine (PE) and in vivo by subjecting the mice to transverse aortic constriction (TAC).

Key findings

TET2 expression was elevated in cardiac tissues in animal models of cardiac hypertrophy, in cardiomyocytes exposed to pro-hypertrophic stimuli, and in HF patients. TET2 knockdown dampened the hypertrophic response in cultured cardiomyocytes treated with different pro-hypertrophic stimuli. Constitutive deletion of TET2 from cardiomyocytes in mice attenuated pathological hypertrophy and improved heart function in the trans-aortic constriction (TAC) model. In addition, induced deletion of TET2 after the onset of pathological hypertrophy similarly averted the pathogenic progression and rescued the decline of heart function.

Significance

TET2 may play an essential role mediating the hypertrophic response in cardiomyocytes. Screening for small-molecule compounds that selectively target TET2 can be considered as a reasonable approach for the intervention of heart failure.

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双加氧酶TET2调节病理性心肌肥厚

心衰（HF）是心血管疾病最具破坏性的后果之一。无论病因如何，心力衰竭通常以心肌肥厚为前兆。在本研究中，我们研究了心肌细胞特异性缺失10 - 11易位2 （TET2）对心肌肥厚的影响。方法和材料采用血管紧张素II （Ang II）、异丙肾上腺素（ISO）和苯麻素（PE）诱导心肌细胞体外和小鼠主动脉横缩（TAC）诱导心肌肥大的方法。主要发现：在心肌肥厚动物模型、暴露于促肥厚刺激的心肌细胞和心衰患者的心脏组织中，stet2表达升高。TET2敲低可抑制不同促肥厚刺激下培养心肌细胞的肥厚反应。在经主动脉收缩（TAC）模型中，小鼠心肌细胞中TET2的组成性缺失减轻了病理性肥厚，改善了心功能。此外，在病理性肥厚发生后诱导TET2的缺失同样避免了致病性的进展，挽救了心功能的衰退。tet2可能在介导心肌细胞肥厚反应中发挥重要作用。筛选选择性靶向TET2的小分子化合物可被认为是干预心力衰竭的一种合理方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.